Effect of piribedil and its metabolite, S584, on brain lipid peroxidation in vitro and in vivo.
We studied the effect of piribedil (1-3,4-methylendioxybenzyl-4-(2-pyrimidyl) piperazine) and its catechol metabolite, S584 (1-(3,4-dihydroxybenzyl-4-(2-pyrimidinyl)-piperazine), on rat brain lipid peroxidation (a) in vitro in rat synaptosomes and cortical slices after induction of an oxidative stress and (b) in vivo in mouse brain after short-term exposure (two and three 4-h cycles) to O2/CO2 (95%:5%). The metabolite (10[-4]-10[-5] M), but not piribedil, prevented Fe3+-stimulated lipid peroxidation in rat synaptosomes and in rat cortical slices incubated with high oxygen concentrations. Piribedil (7.5 and 30 mg/kg, orally), counteracted the increase in thiobarbituric reactive substances in the brain of mice only when these were exposed to two or three cycles of a high oxygen concentration. S584 (30 mg/kg, orally) reduced thiobarbituric acid reactive substances in brain in mice exposed either to air (control) or to three cycles of a high oxygen concentration. These results suggest that piribedil has an antiperoxidative effect in brain, which may be partly related to the in vivo formation of the catechol metabolite, S584.
Calzi
F
F
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Bellasio
R
R
Guiso
G
G
Caccia
S
S
Tacconi
M T
MT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology; D010891:Piribedil / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; C006113:1-(2-pyrimidyl)-4-(3,4-dihydroxybenzyl)piperazine; D010891:Piribedil; D010100:Oxygen